Novel fungicidal composition and method using benzimidazole derivatives

ABSTRACT

Novel benzimidazole derivatives of the formula ##STR1## wherein R is alkyl of 1 to 2 carbon atoms and R 1  is selected from the group consisting of tetrahydrofurfuryl, a saturated or unsaturated oxygen heterocycle of 4 to 5 carbon atoms and ##STR2## wherein Z is unsaturated hydrocarbon radical of 2 to 4 carbon atoms having at least 2 halogen atoms which possess fungicidal activity.

PRIOR APPLICATION

This application is a division of our copending, commonly assigned U.S.application Ser. No. 398,416 filed Sept. 18, 1973, now U.S. Pat. No.3,932,447.

OBJECTS OF THE INVENTION

It is an object of the invention to provide the novel benzimidazolederivatives of formula I and a process for their preparation.

It is another object of the invention to provide novel fungicidalcompositions.

It is another object of the invention to provide a novel method ofkilling fungi.

These and other objects and advantages of the invention will becomeobvious from the following detailed description.

THE INVENTION

The novel benzimidazole derivatives of the invention have the formula##STR3## wherein R is alkyl of 1 to 2 carbon atoms and R₁ is selectedfrom the group consisting of tetrahydrofurfuryl, a saturated orunsaturated oxygen heterocycle of 4 to 5 carbon atoms and ##STR4##wherein Z is unsaturated hydrocarbon radical of 2 to 4 carbon atomhaving at least 2 halogen atoms.

Examples of R₁ are heterocycles such as tetrahydrofurfuryl, furanyl,pyranyl, dihydropyranyl, tetrahydrofuranyl and tetrahydropyranyl andunsaturated acyl groups such as β,β-dichlorovinylcarbonyl andα,β,β-trichlorovinylcarbonyl, R is methyl or ethyl.

The compounds of formula I can be prepared by reacting a compound of theformula ##STR5## with an isocyanate of the formula

    R.sub.1 -N=C=O                                             III

wherein R and R₁ have the above definitions to obtain the correspondingcompound of formula I. The condensation is preferably effected in anorganic solvent such as tetrahydrofuran in the presence of an organicbase such as 1,4-diazabicyclo (2,2,2) octane.

The 2-benzimidazole carbamic acid esters of formula II can be preparedby the process described in U.S. Pat. No. 2,933,504 and the isocyanatesof formula III can be prepared by known methods.

The novel fungicidal compositions of the invention contain as the activeingredient at least one compound of formula I and may contain one ormore other pesticidal agents. The compositions may be in the form ofpowders, suspensions, emulsions or solutions containing, besides theactive ingredients, non-ionic, cationic or anionic surface activeagents; inert powders such as talc, clays, silicates, Kieselguhr; or avehicle such as water, alcohols, hydrocarbons or other organic solvents,mineral, animal or vegetable oils, etc.

The fungicidal compositions preferably contain 25 to 95% by weight ofthe active compound when a powder for foliar spraying or 2.5 to 99% byweight of active compound when a powder for foliar dusting. An exampleof fungicidal composition in the form of a wettable powder is 25% byweight of methyl1-[3'-(5',6'-dihydropyranyl)]-carbamoyl-2-benzimidazolyl-carbamate, 15%by weight of Ekapersol S (condensation product of sodiumnaphthalenesulfonate), 0.5% by weight of Brecolane NVA (sodiumalkylnaphthalenesulfonate), 34.5% by weight of Zeosil 39 (precipitatedsynthetic hydrated silica) and 25% by weight of Vercoryl S (colloidalkaolin).

The novel method of the invention for killing fungi comprises contactingthe fungi with a fungicidally effective amount of at least one compoundof formula I.

In the following examples there are described several preferredembodiments to illustrate the invention. However, it should beunderstood that the invention is not intended to be limited to thespecific embodiments.

EXAMPLE 1Methyl-1-(4'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamateSTEP A: 4-tetrahydropyranyl-isocyanate

A solution of 121.6 g of 4-tetrahydropyranyl carboxylic acid chloride[J. Pharm. Pharmac., Vol. 15 (1963) p. 167] in 250 ml of toluene wasadded dropwise at 10° C to 60 g of sodium nitride in 150 ml of distilledwater and the mixture was stirred for 2 hours. The organic phase wasrecovered by decantation, was washed with a sodium bicarbonate solution,then with water and dried. The organic solution was heated at 100° C for23/4 hours in the presence of m-dinitrobenzene and heating was continueduntil gas evolution ceased. The solution was concentrated under reducedpressure and the residual oil was distilled to obtain 83.6 g of4-tetrahydropyranyl-isocyanate boiling at 79°-80° C under 23 mm Hg andhaving a refractive index n_(D) ²⁰ = 1.4658.

STEP B: Methyl1-(4'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate

35 g of 4-tetrahydropyranyl-isocyanate were added dropwise to asuspension of 38.4 g of methyl 2-benzimidazolyl-carbamate and 0.3 g of1,4-diazbicyclo (2,2,2) octane in 600 ml of tetrahydrofuran and themixture was stirred at 23° C for 5 hours. The mixture was filtered andthe filtrate was evaporated to dryness under reduced pressure. Theproduct was taken up in isopropyl ether and the crystals formed wererecovered by vacuum filtration. This step was repeated 3 more times andthe crystals were dried under reduced pressure at room temperature toobtain 59 g of methyl1-(4'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate in theform of a white solid decomposing at 252° C.

Analysis: C₁₅ H₁₈ O₄ N₄ Calculated: %C, 56.59, %H, 5.69; %N, 17.6.Found: C, 55.1; H, 5.6; N; 17.7.

I.r. spectrum: presence of carbonyl, aromatic ring, NH and NH/OH

EXAMPLE 2 Methyl1-(2'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate

30 ml of 2-tetrahydropyranyl-isocyanate were added to a suspension of 30g of methyl 2-benzimidazolyl-carbamate in 600 ml of tetrahydrofuran andthe mixture was stirred for 5 hours at room temperature and was thenfiltered. The filtrate was evaporated to dryness under reduced pressureand the residue was taken up in hexane. The mixture was vacuum filteredand the product was dried under reduced pressure to obtain 50 g ofmethyl 1-(2'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate inthe form of a white solid decomposing at 236° C.

Analysis: C₁₅ H₁₈ N₄ O₄ Calculated: %C, 56.59; %H, 5.69; %N, 17.60.Found: C, 56.3; H, 5.5; N, 17.2.

I.r. spectrum: presence of carbonyl, NH/OH, C=N and C--O--C

EXAMPLE 3 Methyl1-[3'-(5',6'-dihydropyranyl)]-carbamoyl-2-benzimidazolyl-carbamate STEPA: 3-)5,6-dihydropyranyl)-isocyanate

A solution of 61.5 g of sodium nitrite in 185 ml of distilled waterstood for 16 hours at 0° C and then a solution of 119 g of3-(5,6-dihydroyranyl)-carboxylic acid chloride in 370 ml of toluene wasadded dropwise thereto at 5° C. The mixture was stirred for 15 minutesand was decanted. The toluene phase was washed at 0° C with a 10%aqueous sodium carbonate solution, then with water and dried at 5° C.2.14 g of m-dinitrobenzene were added and the mixture was heated at 130°C with stirring for 3 hours. After standing for 16 hours at 0° C, themixture was distilled to obtain 20 g of3-(5,6-dihydropyranyl)-isocyanate as a colorless oil boiling at 76° Cunder 16 mm Hg and having a refractive index n_(D) ²⁰ = 1.4872.

STEP B: Methyl 1-[3'-(5',6'-dihydropyranyl)]-carbamoyl-2-benzimidazolyl-carbamate

15 g of 3-(5,6-dihydropyranyl)-isocyanate were added to 20 g of methyl2-benzimidazolyl-carbamate and 0.2 g of 1,4-diazabicyclo (2,2,2) octanein 400 ml of tetrahydrofuran and the mixture was stirred for 17 hours atroom temperature and then was filtered. The filtrate was evaporated todryness under reduced pressure and the dry extract was taken up inisopropyl ether. The mixture was vacuum filtered and the precipitate wasdried to obtain 9.8 g of methyl1-[3'-(5',6'-dihydropyranyl)]-carbamoyl-2-benzimidazolyl-carbamatedecomposing at 218° C.

Analysis: C₁₅ H₁₆ N₄ O₄ Calculated: %C, 56.96; %H, 5.1; %N, 17.71;Found: C, 55.9; H, 5.3; N, 16.5;

EXAMPLE 4 Methyl1-(2'-tetrahydrofurfuryl)-carbamoyl-2-benzimidazolyl-carbamate STEP A:2-tetrahydrofurfuryl-isocyanate

100 g of phosgene were dissolved by bubbling into 1250 ml of toluene andthen 100 g of tetrahydrofurfurylamine and 0.2 g of dinitrobenzene wereadded dropwise at 12° C to the said solution. The mixture was refluxedfor 5 hours while bubbling phosgene through it and was then evaporatedto dryness. The residue was distilled to obtain 40.5 g of2-tetrahydrofurfuryl-isocyanate as a colorless liquid boiling at 92° Cunder 30 mm Hg and having a refractive index n_(D) ²³ = 1.4520.

STEP B: Methyl1-(2'-tetrahydrofurfuryl)-carbamoyl-2-benzimidazolyl-carbamate

30 g of 2-tetrahydrofurfuryl-isocyanate were added dropwise to asuspension of 30 g of methyl 2-benzimidazolyl-carbamate and 1 g of1,4-diazabicyclo (2,2,2) octane in 300 ml of tetrahydrofuran and themixture was stirred for 20 hours and vacuum filtered to obtain 19 g ofthe desired product melting with decomposition at 140° C. The filtratewas evaporated to dryness under reduced pressure and the residue waswashed with isopropyl ether and dried. The product was purified bydissolution in chloroform and precipitation with hexane to obtain asecond crop of methyl1-(2'tetrahydrofurfuryl)-carbamoyl-2-benzimidazolyl-carbamate as a whitesolid decomposing at 140° C.

Analysis: C₁₅ H₁₈ N₄ O₄ Calculated: %C, 56.6; %H, 5.7; %N, 17.6. Found:C, 56.3; H, 5.7; N, 17.6.

I.r. spectrum: presence of carbonyl, C=N, NH and aromatic type bonds.

EXAMPLE 5 Methyl1-trichloroacryloyl-carbamoyl-2-benzimidazolyl-carbamate STEP A:Trichloroacryloyl-isocyanate

260 ml of oxalyl chloride were added to 225 g of trichloroacrylamide in525 ml of dichloroethane cooled to 2° C and the mixture was held at 0° Cfor 1 hour and then refluxed for 16 hours. The resulting solution wasevaporated under reduced pressure and the residue was distilled toobtain 232 g of trichloroacryloyl-isocyanate boiling at 86° C under 20mm Hg and having a refractive index n_(D) ²³ = 1.538.

STEP B: Methyl 1-trichloroacryloylcarbamoyl-2-benzimidazolyl-carbamate

13.5 g of trichloroacryloyl-isocyanate were added dropwise to 10 g ofmethyl 2-benzimidzolyl-carbamate and 0.1 g of 1,4-diazabicylco (2,2,2)octane in 160 ml of tetrahydrofuran and the mixture was stirred for 17hours at room temperature and was vacuum filtered. The crystals obtainedwere washed with petroleum ether and dried under reduced pressure toobtain 18.2 g of methyl1-trichloroacryloylcarbamoyl-2-benzimidazolyl-carbamate as a solidmelting at 231° C.

Analysis: C₁₃ H₉ Cl₃ N₄ O₄ Calculated: %C, 39.86; %H, 2.33; %N, 14.32;%Cl, 27.16. Found: C. 41.4; H, 3.1; N, 13.6; Cl 26.4.

I.r. spectrum: presence of carbonyl, OH/NH, C=N and aromatic type bonds.

FUNGICIDAL ACTIVITY A. Test against Botrytis cinerea (in liquidnutritive media)

0.5 ml of a suspension of spores of Botrytis cinerea and 0.5 ml of asuspension of the test product were added to 4 ml of a nutritive mediabased on oat meal and the readings were made after storage for 6 days at24° C. The results of Table 1 are expressed as percent of efficacy ascompared to untreated controls. Compound A is methyl1-(4'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate, compoundB is methyl1-(2'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate andcompound C is methyl1-[3'-(5',6'-dihydropyranyl)]carbamoyl-2-benzimidazolyl-carbamate.

                  TABLE I                                                         ______________________________________                                        Concentration in ppm                                                          ______________________________________                                        Compound                                                                              40       20       10     5      1                                     ______________________________________                                        A       100      100      100    100    100                                   B       100      100      100    100    100                                   C       100      100      100    100    100                                   ______________________________________                                    

B. Test against Botrytis cinerea on lettuce leaves

Lettuce leaves were placed in Petrie dishes and were contaminated withpieces of filter paper enriched with a suspension of conidies and theleaves were sprayed with 1 ml of a solution of the test product onto thesurface of the Petrie dishes having 100 mm diameter. For inoculation, asuspension of 100,000 conidies per ml of carrot juice was used and thecontamination was effected on 4 points of each leaf with confettiimpregnated with the conidies suspension. 5 leaves were used for eachconcentration and after storage for 5 days at 15° C, readings were takenat each point of attack and the results are expressed in Table 2 aspercent of efficacy.

                  TABLE 2                                                         ______________________________________                                               Concentration in ppm                                                   ______________________________________                                        Compound 125       62.5      31.2    15.6                                     ______________________________________                                        A        100       100       100     50                                       B         30       50        20      --                                       C         95       70        45      25                                       ______________________________________                                    

C. Test against Fusarium roseum

5 ml of a suspension of the test product and spores of Fusarium roseumplaced on cellulose pellets were added to 45 ml of a gelose nutritivemedia and after 7 days of growth, the average diameter of the colonieswas compared to the untreated controls. The results of Table 3 areexpressed as percent of efficacy.

                  TABLE 3                                                         ______________________________________                                               Concentration in ppm                                                   ______________________________________                                        Compound 40       20       10     5     1                                     ______________________________________                                        A        100      100      100    90    20                                    B        100      100      100    80    0                                     C        100      40       80     40    40                                    ______________________________________                                    

D. Fungicidal activity against Phytophtora infestans

St. Pierre tomato leaves were kept alive and treated by inoculation bydepositing drops of a conidies suspension. The leaves were then sprayedwith the active compound at dosages of 1000, 500, 250 and 125 ppm at arate of 0.5 ml per container with a diameter of 100 mm. The leaves werecontaminated with a suspension of Phytophtora infestans in sterile watercontaining 100,000 conidies per ml at 4 different points of the leaveand with 5 leaves for each concentration. After storage for 5 days at18° C, the mildew spots appearing at the points of inoculation werecounted and the results are reported in Table 4 as the percentage ofefficacy.

                  TABLE 4                                                         ______________________________________                                               Concentration in ppm                                                   ______________________________________                                        Compound 1000      500       250     125                                      ______________________________________                                        A        60        30        30      0                                        B        70        45        40      30                                       C        55        10        5       0                                        ______________________________________                                    

E. Test against Erysiphe polygoni

Cotyledonous leaves of cucumbers treated with the test product werecontaminated with pieces of filter paper with spores of Erysiphepolygoni. Treatment was effected by spraying the cotyledonous leaves ofcucumbers in pots with 1 ml per surface of pot with a 11 cm diameter.The spore suspension was made of sterile water containing 100,000conidies per ml. 3 pots of 4 to 5 plants each were used for eachconcentration and the pots were stored at 20° C for 12 days. The degreeof attack was noted to permit to show the activity. The results of Table5 are expressed in percent of efficacy.

                  TABLE 5                                                         ______________________________________                                        Concentration in ppm                                                          ______________________________________                                        Compound                                                                              750        375       187.5   93.7                                                                             46.8                                  ______________________________________                                        A       100      30       100    92     92                                    B       100      100      100    92     17                                    C       100      100       17    --     --                                    ______________________________________                                    

The results of Tables 1 to 5 show that compounds A, B and C possessinteresting fungicidal activity against the organisms tested.

Various modifications of the products and processes of the invention maybe made without departing from the spirit or scope thereof and it shouldbe understood that the invention is intended to be limited only asdefined in the appended claims.

We claim:
 1. A method of killing fungi comprising contacting fungi witha fungicidally effective amount of at least one active compound of theformula ##STR6## wherein R is alkyl of 1 to 2 carbon atoms and R₁ isselected from the group consisting of tetrahydrofurfuryl, pyranyl,dihydropyranyl, tetrahydropyranyl and tetrahydrofuranyl.
 2. The methodof claim 1 wherein the active compound is methyl1-(4'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate.
 3. Themethod of claim 1 wherein the active compound is methyl1-(2'-tetrahydropyranyl)-carbamoyl-2-benzimidazolyl-carbamate.
 4. Themethod of claim 1 wherein the active compound is methyl1-[3'-(5',6'-dihydropyranyl)]-carbamoyl-2-benzimidazolyl-carbamate. 5.The method of claim 1 wherein the compound is methyl1-(2'-tetrahydrofurfuryl)-carbamoyl-2-benzimidazolyl-carbamate.
 6. Afungicidal composition comprising a funigicidally effective amount of atleast one compound of the formula ##STR7## wherein R is alkyl of 1 to 2carbon atoms and R₁ is selected from the group consisting oftetrahydrofurfuryl, pyranyl, dihydropyranyl, tetrahydropyranyl andtetranydrofuranyl and a carrier.